title: Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors.
abstract: In order to find the new potent CK2 inhibitors the 60 derivatives of 2-aminopyrimidinone and their 6-aza-substituted analogs were synthesized and tested in vitro. Among them, the most efficient inhibitor 2-hydroxy-5-[4-(4-methoxyphehyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino] benzoic acid was identified (IC50 = 1.1 μM). The structure--activity relationship study of newly synthesized derivatives was carried out and their binding mode with adenosine triphosphate-acceptor site of CK2 was proposed.
authors.affiliation: Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine .
authors.forename: Maksym O
authors.initials: MO
authors.lastname: Chekanov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Ostrynska
authors.forename: Sergii S
authors.initials: SS
authors.lastname: Tarnavskyi
authors.forename: Anatoliy R
authors.initials: AR
authors.lastname: Synyugin
authors.forename: Nadiia V
authors.initials: NV
authors.lastname: Briukhovetska
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Pashenko
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Fokin
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
mesh_terms: D000636:Aminosalicylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000595853:2-hydroxy-5-(4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzoic acid; D000636:Aminosalicylic Acids; D001372:Aza Compounds; D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; D047390:Casein Kinase II
keywords: Aza-pyrimidinones; CK2 inhibitors; chemical optimization; combinatorial synthesis; molecular docking; pyrimidinones; receptor-based virtual screening